Human fetal hemoglobin (HbF) differs from HbA in both functional and structural aspects. these differences are evidence by the weaker affinity of HbF for 2,3-diphosphoglyceric acid, by the non-participation of HbF in gel formation with HbS, and by the incomplete crossreactivity between antisera to HbF and other hemoglobins. We are using immunoabsorption with hemoglobin A to isolate nonprescipitating antibodies specific for the delta chains of hemoglobin F which do not cross react with HbA or other hemoglobins. A radioimmunoassay using reductively methylated 3 (H)-hemoglobin F, non-homologous hemoglobins and synthetic peptides from regions of the delta chains has been used to assess the specificity of binding. The antibodies have been used to quantitate small amounts of HbF in standard laboratory procedures, in erythroid cell cultures and in prenatal diagnosis of hemoglobinopathies.